Dimerization-dependent serine protease activity of FAM111A prevents replication fork stalling at topoisomerase 1 cleavage complexes.

FAM111A, a serine protease, plays roles in DNA replication and antiviral defense. Missense mutations in the catalytic domain cause hyper-autocleavage and are associated with genetic disorders with developmental defects. Despite the enzyme's biological significance, the molecular architecture of the FAM111A serine protease domain (SPD) is unknown. Here, we show that FAM111A is a dimerization-dependent protease containing a narrow, recessed active site that cleaves substrates with a chymotrypsin-like specificity. X-ray crystal structures and mutagenesis studies reveal that FAM111A dimerizes via the N-terminal helix within the SPD. This dimerization induces an activation cascade from the dimerization sensor loop to the oxyanion hole through disorder-to-order transitions. Dimerization is essential for proteolytic activity in vitro and for facilitating DNA replication at DNA-protein crosslink obstacles in cells, while it is dispensable for autocleavage. These findings underscore the role of dimerization in FAM111A's function and highlight the distinction in its dimerization dependency between substrate cleavage and autocleavage.

Inhibition of Plasmodium falciparum plasmepsins by drugs targeting HIV-1 protease: A way forward for antimalarial drug discovery.

Plasmodium species are causative agents of malaria, a disease that is a serious global health concern. FDA-approved HIV-1 protease inhibitors (HIV-1 PIs) have been reported to be effective in reducing the infection by Plasmodium parasites in the population co-infected with both HIV-1 and malaria. However, the mechanism of HIV-1 PIs in mitigating Plasmodium pathogenesis during malaria/HIV-1 co-infection is not fully understood. In this study we demonstrate that HIV-1 drugs ritonavir (RTV) and lopinavir (LPV) exhibit the highest inhibition activity against plasmepsin II (PMII) and plasmepsin X (PMX) of P. falciparum. Crystal structures of the complexes of PMII with both drugs have been determined. The inhibitors interact with PMII via multiple hydrogen bonding and hydrophobic interactions. The P4 moiety of RTV forms additional interactions compared to LPV and exhibits conformational flexibility in a large S4 pocket of PMII. Our study is also the first to report inhibition of P. falciparum PMX by RTV and the mode of binding of the drug to the PMX active site. Analysis of the crystal structures implies that PMs can accommodate bulkier groups of these inhibitors in their S4 binding pockets. Structurally similar active sites of different vacuolar and non-vacuolar PMs suggest the potential of HIV-1 PIs in targeting these enzymes with differential affinities. Our structural investigations and biochemical data emphasize PMs as crucial targets for repurposing HIV-1 PIs as antimalarial drugs.

Microbial communities drive flux of acid orange 7 and crystal violet dyes in water-sediment system.

Unchecked dye effluent discharge poses escalating environmental and economic concerns, especially in developing nations. While dyes are well-recognized water pollutants, the mechanisms of their environmental spread are least understood. Therefore, the present study examines the partitioning of Acid Orange 7 (AO7) and Crystal Violet (CV) dyes using water-sediment microcosms and reports that native microbes significantly affect AO7 decolorization and transfer. Both dyes transition from infused to pristine matrices, reaching equilibrium in a fortnight. While microbes influence CV partitioning, their role in decolorization is minimal, emphasizing their varied impact on the environmental fate of dyes. Metagenomic analyses reveal contrasting microbial composition between control and AO7-infused samples. Control water samples displayed a dominance of Proteobacteria (62%), Firmicutes (24%), and Bacteroidetes (9%). However, AO7 exposure led to Proteobacteria reducing to 57% and Bacteroidetes to 3%, with Firmicutes increasing to 34%. Sediment samples, primarily comprising Firmicutes (47%) and Proteobacteria (39%), shifted post-AO7 exposure: Proteobacteria increased to 53%, and Firmicutes dropped to 38%. At the genus level, water samples dominated by Niveispirillum (34%) declined after AO7 exposure, while Bacillus and Pseudomonas increased. Notably, Serratia and Sphingomonas, known for azo dye degradation, rose post-exposure, hinting at their role in AO7 decolorization. Conversely, sediment samples showed a decrease in the growth of Bacillus and an increase in that of Pseudomonas and Serratia. These findings emphasize the significant role of microbial communities in determining the environmental fate of dyes, providing insights on its environmental implications and management.

Regulation and safety measures for nanotechnology-based agri-products.

There is a wide range of application for nanotechnology in agriculture, including fertilizers, aquaculture, irrigation, water filtration, animal feed, animal vaccines, food processing, and packaging. In recent decades, nanotechnology emerged as a prospective and promising approach for the advancement of Agri-sector such as pest/disease prevention, fertilizers, agrochemicals, biofertilizers, bio-stimulants, post-harvest storage, pheromones-, and nutrient-delivery, and genetic manipulation in plants for crop improvement by using nanomaterial as a carrier system. Exponential increase in global population has enhanced food demand, so to fulfil the demand markets already included nano-based product likewise nano-encapsulated nutrients/agrochemicals, antimicrobial and packaging of food. For the approval of nano-based product, applicants for a marketing approval must show that such novel items can be used safely without endangering the consumer and environment. Several nations throughout the world have been actively looking at whether their regulatory frameworks are suitable for handling nanotechnologies. As a result, many techniques to regulate nano-based products in agriculture, feed, and food have been used. Here, we have contextualized different regulatory measures of several countries for nano-based products in agriculture, from feed to food, including guidance and legislation for safety assessment worldwide.

Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls: p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls, which is further validated by enzyme-linked immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.

Ecological life strategies of microbes in response to antibiotics as a driving factor in soils.

Antibiotics as a selection pressure driving the evolution of soil microbial communities is not well understood. Since microbial functions govern ecosystem services, an ecological framework is required to understand and predict antibiotic-induced functional and structural changes in microbial communities. Therefore, metagenomic studies explaining the impacts of antibiotics on soil microbial communities were mined, and alterations in microbial taxa were analyzed through an ecological lens using Grimes's Competitor-Stress tolerator-Ruderal (CSR) model. We propose considering antibiotics as the primary abiotic factor mentioned in the CSR model and classifying non-susceptible microbial taxa as degraders, resistant, and resilient groups analogous to competitors, stress tolerators, and ruderal strategists, respectively. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were among the phyla harboring most members with antibiotic-resistant groups. However, some antibiotic-resistant microbes in these phyla could not only tolerate but also subsist solely on antibiotics, while others degraded antibiotics as a part of secondary metabolism. Irrespective of their taxonomic affiliation, microbes with each life strategy displayed similar phenotypic characteristics. Therefore, it is recommended to consider microbial functional traits associated with each life strategy while analyzing the ecological impacts of antibiotics. Also, potential ecological crises posed by antibiotics through changes in microbial community and ecosystem functions were visualized. Applying ecological theory to understand and predict antibiotics-induced changes in microbial communities will also provide better insight into microbial behavior in the background of emerging contaminants and help develop a robust ecological classification system of microbes.

Iron-dependent mutualism between Chlorella sorokiniana and Ralstonia pickettii forms the basis for a sustainable bioremediation system.

Phototrophic communities of autotrophic microalgae and heterotrophic bacteria perform complex tasks of nutrient acquisition and tackling environmental stress but remain underexplored as a basis for the bioremediation of emerging pollutants. In industrial monoculture designs, poor iron uptake by microalgae limits their productivity and biotechnological efficacy. Iron supplementation is expensive and ineffective because iron remains insoluble in an aqueous medium and is biologically unavailable. However, microalgae develop complex interkingdom associations with siderophore-producing bacteria that help solubilize iron and increase its bioavailability. Using dye degradation as a model, we combined environmental isolations and synthetic ecology as a workflow to design a simplified microbial community based on iron and carbon exchange. We established a mutualism between the previously non-associated alga Chlorella sorokiniana and siderophore-producing bacterium Ralstonia pickettii. Siderophore-mediated increase in iron bioavailability alleviated Fe stress for algae and increased the reductive iron uptake mechanism and bioremediation potential. In exchange, C. sorokiniana produced galactose, glucose, and mannose as major extracellular monosaccharides, supporting bacterial growth. We propose that extracellular iron reduction by ferrireductase is crucial for azoreductase-mediated dye degradation in microalgae. These results demonstrate that iron bioavailability, often overlooked in cultivation, governs microalgal growth, enzymatic processes, and bioremediation potential. Our results suggest that phototrophic communities with an active association for iron and carbon exchange have the potential to overcome challenges associated with micronutrient availability, while scaling up bioremediation designs.

Achilles Tendon Softness and Thickness in Patients With Hypercholesterolemia.

Background Hypercholesterolemia is a condition where blood levels of cholesterol are high. It is of two types: The first type is familial hypercholesterolemia, which is hereditary, and the second one is due to diseases like diabetes, thyroid, etc. Achilles tendon xanthomas are noted in both types of hypercholesterolemia, which can be used as an indicator that predicts early cardiovascular disease. The aim of the study is to estimate the Achilles tendon thickness (ATT) and softness among hypercholesterolemia patients and to find the correlation between ATT and total cholesterol. Methodology A hospital-based cross-sectional, analytical study was done in a tertiary care hospital, Salem, for eight months. Patients of age over 18 years of both sexes who came for screening of total cholesterol in the outpatient department were included in the study. Those patients with a history of previous leg injury involving the Achilles tendon were excluded from the study. A pre-structured questionnaire was used to collect the data, and analysis was done using Statistical Package for the Social Sciences (SPSS) v20 (IBM Corp., Armonk, NY). The analysts performed the Pearson correlation test to determine the correlation between two continuous variables. A p-value of less than 0.05 was used to indicate statistical significance. Results In this study, there are 40 participants in the normal group and about 60 participants in the secondary hypercholesterolemia group. The mean ATT value among males and females was 9.3 and 6.1 mm, respectively. A positive correlation was noted between the ATT and total cholesterol value (p-value = 0.0001). Conclusion The thickness and softness of the Achilles tendon are positively correlated with the serum total cholesterol level. Males are the group where this correlation is most significant. As a result, men have a higher risk of developing Achilles tendon thickening than women. The thickness of the Achilles tendon can therefore be one of the early signs of high cholesterol levels. The clinician can utilize this indicator to evaluate early abnormal cardiac illness.

Patent intelligence of RNA viruses: Implications for combating emerging and re-emerging RNA virus based infectious diseases.

The recent outbreak of one of the RNA viruses (2019-nCoV) has affected most of the population and the fatalities reported may label it as a modern-day scourge. Active research on RNA virus infections and vaccine development had more commercial impact which leads to an increase in patent filings. Patents are a goldmine of information whose mining yields crucial technological inputs for further research. In this research article, we have investigated both the patent applications and granted patents, to identify the technological trends and their impact on 2019-nCoV infection using biotechnology-related keywords such as genes, proteins, nucleic acid etc. related to the RNA virus infection. In our research, patent analysis was majorly focused on prospecting for patent data related to the RNA virus infections. Our patent analysis specifically identified spike protein (S protein) and nucleocapsid proteins (N proteins) as the most actively researched macromolecules for vaccine and/or drug development for diagnosis and treatment of RNA virus based infectious diseases. The outcomes of this patent intelligence study will be useful for the researchers who are actively working in the area of vaccine or drug development for RNA virus-based infections including 2019-nCoV and other emerging and re-emerging viral infections in the near future.

Mechanism of apoptosis activation by Curcumin rescued mutant p53Y220C in human pancreatic cancer.

The mutant p53Y220C (mutp53Y220C) is frequently observed in numerous tumors, including pancreatic cancer. The mutation creates a crevice in the DNA binding core domain and makes p53 a thermally unstable non-functional protein that assists tumor progression and confers resistance to chemotherapeutic drugs. Restoring mutp53 function to its wild type by selectively targeting this crevice with small molecules is a pivotal strategy to promote apoptosis. In this study, we have shown through different biophysical and cell-based studies that curcumin binds and rescues mutp53Y220C to an active wild-type conformation and restores its apoptotic transcription function in BxPC-3-pancreatic cancer cells. In addition, the curcumin-rescued-p53Y220C (CRp53) showed significant hyperphosphorylation at Ser15, Ser20, and acetylation at Lys382 with an 8-fold increase in transcription activity in the BxPC-3 cell lines. We also observed that the active CRp53 escapes Mdm2-mediated proteasomal degradation and the majority of the proteins were localized inside the nucleus with an increased half-life and transcription restoration compared to untreated BxPC-3 cells. By label-free proteomics analysis, we observed that upon curcumin treatment almost 227 proteins were dysregulated with the majority of them being transcriptional targets of p53. Based on our studies, it reflects that apoptosis in pancreatic cancer cells is mediated by curcumin-rescued mutant p53Y220C.

Progranulin Preserves Autophagy Flux and Mitochondrial Function in Rat Cortical Neurons Under High Glucose Stress.

Chronic hyperglycemia in type II diabetes results in impaired autophagy function, accumulation of protein aggregates, and neurodegeneration. However, little is known about how to preserve autophagy function under hyperglycemic conditions. In this study, we tested whether progranulin (PGRN), a neurotrophic factor required for proper lysosome function, can restore autophagy function in neurons under high-glucose stress. We cultured primary cortical neurons derived from E18 Sprague-Dawley rat pups to maturity at 10 days in vitro (DIV) before incubation in high glucose medium and PGRN for 24-72 h before testing for autophagy flux, protein turnover, and mitochondrial function. We found that although PGRN by itself did not upregulate autophagy, it attenuated impairments in autophagy seen under high-glucose conditions. Additionally, buildup of the autophagosome marker light chain 3B (LC3B) and lysosome marker lysosome-associated membrane protein 2A (LAMP2A) changed in both neurons and astrocytes, indicating a possible role for glia in autophagy flux. Protein turnover, assessed by remaining advanced glycation end-product levels after a 6-h incubation, was preserved with PGRN treatment. Mitochondrial activity differed by complex, although PGRN appeared to increase overall activity in high glucose. We also found that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3ß (GSK3ß), kinases implicated in autophagy function, increased with PGRN treatment under stress. Together, our data suggest that PGRN prevents hyperglycemia-induced decreases in autophagy by increasing autophagy flux via increased ERK1/2 kinase activity in primary rat cortical neurons.

Inter-subunit crosstalk via PDZ synergistically governs allosteric activation of proapoptotic HtrA2.

The mitochondrial serine protease High-temperature requirement A2 (HtrA2) is associated with various diseases including neurodegenerative disorders and cancer. Despite availability of structural details, the reports on HtrA2's mechanistic regulation that varies with the type of activation signals still remain non-concordant. To expound the role of regulatory PDZ (Postsynaptic density-95/Discs large/Zonula occludens-1) domains in multimodal activation of HtrA2, we generated heterotrimeric HtrA2 variants comprising different numbers of PDZs and/or active-site mutations. Sequential deletion of PDZs from the trimeric ensemble significantly affected its residual activity in a way that proffered a hypothesis advocating inter-molecular allosteric crosstalk via PDZs in HtrA2. Furthermore, structural and computational snapshots affirmed the role of PDZs in secondary structural element formation around the regulatory loops and coordinated reorganization of the N-terminal region. Therefore, apart from providing cues for devising structure-guided therapeutic strategies, this study establishes a physiologically relevant working model of complex allosteric regulation through a trans-mediated cooperatively shared energy landscape.

Ecotoxic effects of microplastics and contaminated microplastics - Emerging evidence and perspective.

The high prevalence and persistence of microplastics (MPs) in pristine habitats along with their accumulation across environmental compartments globally, has become a matter of grave concern. The resilience conferred to MPs using the material engineering approaches for outperforming other materials has become key to the challenge that they now represent. The characteristics that make MPs hazardous are their micro to nano scale dimensions, surface varied wettability and often hydrophobicity, leading to non-biodegradability. In addition, MPs exhibit a strong tendency to bind to other contaminants along with the ability to sustain extreme chemical conditions thus increasing their residence time in the environment. Adsorption of these co-contaminants leads to modification in toxicity varying from additive, synergistic, and sometimes antagonistic, having consequences on flora, fauna, and ultimately the end of the food chain, human health. The resulting environmental fate and associated risks of MPs, therefore greatly depend upon their complex interactions with the co-contaminants and the nature of the environment in which they reside. Net outcomes of such complex interactions vary with core characteristics of MPs, the properties of co-contaminants and the abiotic factors, and are required to be better understood to minimize the inherent risks. Toxicity assays addressing these concerns should be ecologically relevant, assessing the impacts at different levels of biological organization to develop an environmental perspective. This review analyzed and evaluated 171 studies to present research status on MP toxicity. This analysis supported the identification and development of research gaps and recommended priority areas of research, accounting for disproportionate risks faced by different countries. An ecological perspective is also developed on the environmental toxicity of contaminated MPs in the light of multi-variant stressors and directions are provided to conduct an ecologically relevant risk assessment. The presented analyses will also serve as a foundation for developing environmentally appropriate remediation methods and evaluation frameworks.

Ribosome inactivating proteins - An unfathomed biomolecule for developing multi-stress tolerant transgenic plants.

Transgenic crops would serve as a tool to overcome the forthcoming crisis in food security and environmental safety posed by degrading land and changing global climate. Commercial transgenic crops developed so far focus on single stress; however, sustaining crop yield to ensure food security requires transgenics tolerant to multiple environmental stresses. Here we argue and demonstrate the untapped potential of ribosome inactivating proteins (RIPs), translation inhibitors, as potential transgenes in developing transgenics to combat multiple stresses in the environment. Plant RIPs target the fundamental processes of the cell with very high specificity to the infecting pests. While controlling pathogens, RIPs also cause ectopic expression of pathogenesis-related proteins and trigger systemic acquired resistance. On the other hand, during abiotic stress, RIPs show antioxidant activity and trigger both enzyme-dependent and enzyme-independent metabolic pathways, alleviating abiotic stress such as drought, salinity, temperature, etc. RIPs express in response to specific environmental signals; therefore, their expression obviates additional physiological load on the transgenic plants instead of the constitutive expression. Based on evidence from its biological significance, ecological roles, laboratory- and controlled-environment success of its transgenics, and ethical merits, we unravel the potential of RIPs in developing transgenic plants showing co-tolerance to multiple environmental stresses.

Heavy metal pollution and risks in a highly polluted and populated Indian river-city pair using the systems approach.

A sectorial approach for assessing heavy metal pollution in rivers neglects the inter-relationship between its environmental compartments and thus fails to report realistic pollution status and associated ecological and human health risks. Therefore, a systems approach was adopted to assess heavy metal pollution and associated risks in the Yamuna River (Delhi, India), one of the world's most polluted and populated river-city pairs. Sampling sites selected along the river with distinct land use were uncultivated natural floodplain vegetation, marshy area, invasive community, arable land, and human settlements. The multivariate analysis identified sources of pollutions (Pb, Cd, Cr, and Ni [anthropogenic]; Fe and Zn [geogenic]). Across the land use, a high log Kp value of Zn and Pb in water-soil phase than in water-sediment phase indicates their long-range transfer, whereas low log Kp (water-soil) of Cd suggests river sediments as its reservoirs. Comparison of pollution indices of Cd, Cr, and Pb in water, sediment, and soil across the land use suggested the role of vegetation in reducing pollution in the environment. Ecological risk also gets reduced progressively from water to sediment to the soil in naturally vegetated sites. Similarly, in river water, Cr, Cd, Ni, and Pb pose carcinogenic and non-carcinogenic risks to adults and children, which are also reduced in sediments and soil of different vegetation regimes. This study showed the eco-remediation services rendered by natural vegetation in reducing pollution and associated ecological and human health risks. To conclude, using a systems approach has significance in assessing pollution at the ecosystem level, and focusing on riverbank land use remains significant in developing methods to reduce pollution and ecological and human health risks for sustainable riverbank management.

Comparative analysis of inter-observer variability between conventional reporting system of salivary gland cytology with Milan system for reporting salivary gland cytopathology.

BACKGROUND: Interpretation of salivary gland cytology often leads to inter-observer variability due to heterogenous and complex nature of these lesions. This creates a dilemma regarding their management by clinicians. Proposal of a universal system of reporting of salivary gland lesions leading to agreement in diagnosis and better understanding among clinicians was the need of the hour. Hence Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed in 2015 by the American society of cytopathology and the International Academy of Cytology. Present study was undertaken to assess inter-observer variability in reporting by conventional system and MSRSGC. MATERIAL AND METHODS: One hundred and seventy-six cases of salivary gland lesions were subjected to fine needle aspiration cytology. Cases were interpreted by two experienced cytopathologists and were reported by both conventional system and MSRSGC. Histopathological correlation was available in 81 cases. RESULTS: Inter-observer variability was noted in six cases reported by conventional system and in two cases by MSRSGC. Moreover three cases out six cases had different management protocols while both cases of Milan system for reporting salivary gland cytology had same management. Thirteen cases diagnosed by Milan system and 17 cases diagnosed by conventional system were discordant with histopathological diagnosis. CONCLUSION: Milan system for reporting salivary gland cytology has an edge over conventional system of reporting as it provides better agreement among cytopathologists and better management guidelines for clinicians with the added advantage of assessment of risk of malignancy.

Nano-enabled sensing of per-/poly-fluoroalkyl substances (PFAS) from aqueous systems - A review.

Per-/poly-fluoroalkyl substances (PFAS) are an emerging class of environmental contaminants used as an additive across various commodity and fire-retardant products, for their unique thermo-chemical stability, and to alter their surface properties towards selective liquid repellence. These properties also make PFAS highly persistent and mobile across various environmental compartments, leading to bioaccumulation, and causing acute ecotoxicity at all trophic levels particularly to human populations, thus increasing the need for monitoring at their repositories or usage sites. In this review, current nano-enabled methods towards PFAS sensing and its monitoring in wastewater are critically discussed and benchmarked against conventional detection methods. The discussion correlates the materials' properties to the sensitivity, responsiveness, and reproducibility of the sensing performance for nano-enabled sensors in currently explored electrochemical, spectrophotometric, colorimetric, optical, fluorometric, and biochemical with limits of detection of 1.02 × 10-6 µg/L, 2.8 µg/L, 1 µg/L, 0.13 µg/L, 6.0 × 10-5 µg/L, and 4.141 × 10-7 µg/L respectively. The cost-effectiveness of sensing platforms plays an important role in the on-site analysis success and upscalability of nano-enabled sensors. Environmental monitoring of PFAS is a step closer to PFAS remediation. Electrochemical and biosensing methods have proven to be the most reliable tools for future PFAS sensing endeavors with very promising detection limits in an aqueous matrix, short detection times, and ease of fabrication.

Microbial fuel cells for mineralization and decolorization of azo dyes: Recent advances in design and materials.

Microbial fuel cells (MFCs) exhibit tremendous potential in the sustainable management of dye wastewater via degrading azo dyes while generating electricity. The past decade has witnessed advances in MFC configurations and materials; however, comprehensive analyses of design and material and its association with dye degradation and electricity generation are required for their industrial application. MFC models with high efficiency of dye decolorization (96-100%) and a wide variation in power generation (29.4-940 mW/m2) have been reported. However, only 28 out of 104 studies analyzed dye mineralization - a prerequisite to obviate dye toxicity. Consequently, the current review aims to provide an in-depth analysis of MFCs potential in dye degradation and mineralization and evaluates materials and designs as crucial factors. Also, structural and operation parameters critical to large-scale applicability and complete mineralization of azo dye were evaluated. Choice of materials, i.e., bacteria, anode, cathode, cathode catalyst, membrane, and substrate and their effects on power density and dye decolorization efficiency presented in review will help in economic feasibility and MFCs scalability to develop a self-sustainable solution for treating azo dye wastewater.

Structures of plasmepsin X from Plasmodium falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme.

Plasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme is involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites.

Advancements in macromolecular crystallography: from past to present.

Protein Crystallography or Macromolecular Crystallography (MX) started as a new discipline of science with the pioneering work on the determination of the protein crystal structures by John Kendrew in 1958 and Max Perutz in 1960. The incredible achievements in MX are attributed to the development of advanced tools, methodologies, and automation in every aspect of the structure determination process, which have reduced the time required for solving protein structures from years to a few days, as evident from the tens of thousands of crystal structures of macromolecules available in PDB. The advent of brilliant synchrotron sources, fast detectors, and novel sample delivery methods has shifted the paradigm from static structures to understanding the dynamic picture of macromolecules; further propelled by X-ray Free Electron Lasers (XFELs) that explore the femtosecond regime. The revival of the Laue diffraction has also enabled the understanding of macromolecules through time-resolved crystallography. In this review, we present some of the astonishing method-related and technological advancements that have contributed to the progress of MX. Even with the rapid evolution of several methods for structure determination, the developments in MX will keep this technique relevant and it will continue to play a pivotal role in gaining unprecedented atomic-level details as well as revealing the dynamics of biological macromolecules. With many exciting developments awaiting in the upcoming years, MX has the potential to contribute significantly to the growth of modern biology by unraveling the mechanisms of complex biological processes as well as impacting the area of drug designing.